PROJECT SUMMARY/ABSTRACT Diabetes mellitus is a major risk factor for tendon problems and abnormalities. Tendons, which connect muscle to bone, are critical for optimal musculoskeletal function. The prevalence rates of tendon abnormalities and degeneration in diabetics have been reported as high as 89%, and some of these individuals are asymptomatic, despite the presence of structural tendon abnormalities. The functional integrity of tendon is largely dependent on the high collagen content and linear arrangement of collagen at the fibril level. Both of these properties appear to be altered in diabetic tendinopathy. Diabetic tendinopathies are pervasive and disabling, but little is known about their pathogenesis, which has hampered the development of effective therapies for these conditions. While evidence describing changes to tendon with diabetes is documented, our understanding of this process is severely limited. In order to provide effective therapeutic options to reduce tendon degeneration and associate sequela in diabetic patients, it is important that we expand our understanding of the mechanisms contributing to tendinopathies in this large patient population. Uniquely, these studies propose human subjects' research to investigate the role of advance glycation end- products (AGEs) on tendon fibril disorganization and degradation with diabetes and aim to provide some of the first human data examining the mechanistic and pathological processes contributing to the development of diabetic tendinopathies. Ultimately, the proposed research will be impactful by providing preliminary information for the exploration of novel therapies and treatment strategies to reduce tendon complications associated with AGE formation and diabetes. In parallel, the proposed studies will provide a strong, collaborative, and multifaceted training environment for the applicant. During the completion of the proposed studies, the applicant will be provided with the necessary laboratory and training resources, tailored mentorship, and professional development opportunities to successfully complete the proposed research and training goals. The opportunities and skillsets that will be gained from the proposed study will ensure a successful transition to an independent research scientist.